Natural products of plant endophytes are an untapped promising new resource for drugs having an interesting realm of novel chemistry. Their studies surprisingly reveals that many of the important drugs thought to be produced by plants are probably, the products of their interaction with endophytic microbes residing in tissue between living plant cells. Possessing this incredible adaptability due to their flexible power, they have proved their potential importance, not only in agriculture, industry but, also wonderfully in human health in many therapeutic areas, interestingly unveiling its treasure trove, broadening the landscape of natural product research and discovery. [Annu. Rev. Phytopathol 48: 19.1-19.23 (2010)]. This beautiful mystery of nature as a valuable contributor has taken much of curiosity with deep interest and studies have interestingly unfolded that plants, insects, marine organisms themselves also utilize these natural products to defend themselves against many serious unfavorable biotic and abiotic conditions [Chem Rev 109: 3012-3043 (2009); Nat. Prod. Rep. 24: 1225-1244 (2007)]
Trichoderma, a widely applied filamentous biocontrol fungi, found to produce many beneficial effects on plants has passed through several phases in agricultural applications with each new discovery, only adding more, to its usefulness, has been recently redefined as endophytic plant symbionts, which wonderfully extend their stronger potential in disease control as well [US 2012/0096598; Microbiology 158: 17-25 (2012); Microbiology 158: 35-45 (2012); Microbiology 155: 3371-3381 (2009)]. The metabolomics of Trichoderma species are incredibly complex, the variety and number of secondary metabolites being produced are astonishingly high. Recent study of genome sequences of Trichoderma species has revealed a vast repertoire of genes putatively involved in biosynthesis of secondary metabolites such as Non Ribosomal Peptides, polyketides, terpenoids and pyrones [Nature reviews 2004, 2, 43-56].
Peptaibols, are such unique linear, hydrophobic antibiotic peptides being produced by non-ribosomal peptide synthesases and are proteolytic enzyme-resistant, membrane active peptides, characterized by high content of alpha amino isobutyric acid, isovaline with an N-terminal acyl moiety and C terminus as amino alcohol such as phenylalaninol, valinol or leucinol [J. Nat. Prod. 72: 1036-1044 (2009); J. Biol. Chem. 286, 6: 4544-4554 (2011); Microbiology 153: 3417-3437 (2007)]. Peptide synthetases possess multiple modules that bind, activate and condense each specific amino acid to form the peptide product. The number, organization and order of modules in the peptide synthetase reflect the size of complexity and the sequence of the peptide. It seems that the specificity of each module is variable resulting in the synthesis of micro-heterogeneous mixture. The biological activity of peptaibols has been closely linked to their three dimensional α-helical structures and their potential to form pores in bilayer lipid membranes [J. Nat. Prod. 70: 391-396 (2007); J. Pept. Sci. DOI 10.1002/psc.2425; J. Am. Chem. Soc. 114: 2170-2174(1992); FEM Microbial Lett DOI: 10.1111/febs.12010], antibacterial, antiparasitic [U.S. Pat. No. 6,582,949; U.S. Pat. No. 7,067,112; U.S. Pat. No. 5,432,157], antifungal, occasional antiviral, insecticidal, cyto toxic [J. Nat. Prod. 2008, 71, 1600], antitumor [J.Nat. Prod. 69: 736-741 (2006)], inhibition of mitochondrial ATPase, uncoupling of oxidative phosphorylation, inhibition of platelet aggregation, induction of fungal morphogenesis and neuroleptic effects have also been reported. [J. Nat. Prod. 2001, 64, 164-170].
A Marine strain of Trichoderma longibraciatum isolated from mussels (Mytilus edulis) from estuary of the Loire river from which micro-hetrogenous mixture of 11 residue peptaibols tricholongins A and C were isolated belonging to peptidic family of Ac-Aib-XXX-XXX-XXX-Aib-Pro-XXX-XXX-Aib-Pro-XXol having cytotoxicity on KB cells [Peptides 28: 1351-1358 (2007)]. 19 residue tricholongins BI and B II [M+Na]+ having 1932 and 1946 Da having antifungal and antibacterial activity collected from walls of a beer cellar. [Eur J. Biochem 201: 661-674 (1991)] and 20 residue longibrachins LGB II and LGB III having antimycoplasmic properties [J. Nat. Prod 64: 164-170 (2001)].